Review of policy and status of implementation of collaborative HIV-TB activities in 23 high-burden countries.

REVIEW ARTICLE

INT J TUBERC LUNG DIS 18(10):1149–1158 Q 2014 The Union http://dx.doi.org/10.5588/ijtld.13.0889

Review of policy and status of implementation of collaborative HIV-TB activities in 23 high-burden countries S. Gupta,* R. Granich,* A. Date,† P. Lepere,* B. Hersh,‡ E. Gouws,§ B. Samb* *Special Initiatives, Joint United Nations Programme on HIV/AIDS (UNAIDS), Geneva, Switzerland; †Division for Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, GA, USA; ‡Global Financing Mechanisms and Collaboration Division, UNAIDS, Geneva, Switzerland; §Regional Support Team, Eastern and Southern Africa, UNAIDS, Johannesburg, South Africa SUMMARY

Issuance of national policy guidance is a critical step to ensure quality HIV-TB (human immunodeficiency virustuberculosis) coordination and programme implementation. From the database of the Joint United Nations Programme on HIV/AIDS (UNAIDS), we reviewed 62 national HIV and TB guidelines from 23 high-burden countries for recommendations on HIV testing for TB patients, criteria for initiating antiretroviral therapy (ART) and the Three I’s for HIV/TB (isoniazid preventive treatment [IPT], intensified TB case finding and TB infection control). We used UNAIDS country-level programme data to determine the status of implementation of existing guidance. Of the 23 countries representing 89% of the global HIV-TB burden, Brazil recommends ART irrespective of CD4 count for all people living with HIV, and four (17%) countries recommend ART at the World Health Organization (WHO) 2013 guidelines level of CD4 count 6500 cells/mm3 for asymptomatic persons. Nineteen (83%) countries are consistent with WHO

2013 guidelines and recommend ART for HIV-positive TB patients irrespective of CD4 count. IPT is recommended by 16 (70%) countries, representing 67% of the HIV-TB burden; 12 recommend symptom-based screening alone for IPT initiation. Guidelines from 15 (65%) countries with 79% of the world’s HIV-TB burden include recommendations on HIV testing and counselling for TB patients. Although uptake of ART, HIV testing for TB patients, TB screening for people living with HIV and IPT have increased significantly, progress is still limited in many countries. There is considerable variance in the timing and content of national policies compared with WHO guidelines. Missed opportunities to implement new scientific evidence and delayed adaptation of existing WHO guidance remains a key challenge for many countries. K E Y W O R D S : ART; IPT; HIV testing; Three I’s for HIV/ TB

HUMAN IMMUNODEFICIENCY VIRUS (HIV) and tuberculosis (TB) epidemics present unprecedented public health challenges, with each accentuating the impact of the other. HIV is the single greatest risk factor for developing active TB disease,1 while TB is the leading cause of morbidity and mortality among people living with HIV (PLHIV).2,3 In 2012, there were an estimated 1.1 million cases of TB disease among 35.3 million PLHIV.4 In 2012, the 320 000 deaths among PLHIV comprised 1.3 million (25%) TB deaths and 1.6 million (20%) deaths due to the acquired immune-deficiency syndrome.4,5 As part of the effort to meet the 2015 United Nations (UN) target of reducing HIV-associated TB mortality by 50%,6 there has been a significant scaleup of integrated HIV and TB activities to ensure that 1) TB patients have access to HIV counselling and

testing and HIV prevention and treatment services; and 2) PLHIV accessing HIV services are provided with TB prevention interventions, called the Three I’s for HIV/TB, and early antiretroviral therapy (ART), which include: 1) intensified TB case finding (ICF), 2) isoniazid preventive therapy (IPT), and 3) TB infection control in health care facilities and congregate settings.7 ART is a powerful intervention for preventing TBrelated illness, death and transmission among PLHIV.8–13 A recent World Health Organization (WHO) led meta-analysis showed that ART reduces the risk of TB in PLHIV by approximately 65%.12 The 2010 WHO ART guidelines recommended initiation of ART at a CD4 count of 6350 cells/ mm3 for all HIV-positive asymptomatic persons and for persons with HIV-associated TB irrespective of

Correspondence to: Somya Gupta, Joint United Nations Programme on HIV/AIDS (UNAIDS), Avenue Appia 20, CH-1211, Geneva 27. Tel: (þ91) 98 18 59 81 40. e-mail: [email protected] Article submitted 11 December 2013. Final version accepted 26 April 2014.

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CD4 count.14 In July 2013, the WHO revised its guidelines to recommend initiation of ART at CD4 count 6500 cells/mm3 for asymptomatic HIV-positive persons and irrespective of CD4 count for PLHIV who are the HIV-positive partner in serodiscordant couples, pregnant women, persons diagnosed with TB, children aged ,5 years or persons with hepatitis B infection.15 There is a growing body of literature supporting earlier ART for clinical benefit, including the recently published randomised control HPTN 052 study demonstrating that early ART initiation at CD4 cell count 6550 cells/mm3 had significantly greater health benefits than waiting until the patient is more severely immunocompromised.16 The 2011 WHO ICF/IPT guidelines for PLHIV are designed to facilitate expanded access to IPT for asymptomatic PLHIV, and recommend TB screening using a clinical symptom-based algorithm to determine eligibility for IPT or consideration for further diagnostic workup for TB.17 IPT is recommended for at least 6 months for patients without current cough, fever, weight loss and night sweats, irrespective of degree of immunosuppression, ART use, previous TB treatment and pregnancy. IPT for 36 months or lifelong treatment is conditionally recommended for asymptomatic PLHIV in settings with a high transmission of TB among PLHIV. Due to operational challenges, the tuberculin skin test (TST) is not required for initiating IPT in PLHIV; however, it may be used in settings where it is feasible. The 2009 WHO policy on TB infection control recommends managerial controls, administrative controls, environmental controls and personal protective equipment measures to reduce the risk of TB transmission in health care facilities and congregate settings.18 The strong association of TB with HIV has highlighted the need to link and integrate TB and HIV services in countries severely affected by both epidemics. Issuance of national policy guidance is a critical step in ensuring quality HIV-TB coordination and programme implementation. Using the current WHO guidelines as a reference, this article summarises country-specific guidelines issued by national HIV and TB programmes on HIV testing for TB patients, ART eligibility criteria and the Three I’s for HIV/TB in the countries with the highest HIV and TB burden. The country-level surveillance data of the Joint United Nations Programme on HIV/AIDS (UNAIDS) on progress in programme implementation were used to determine the status of implementation of existing guidance on ART, HIV testing for TB patients, ICF and IPT. This guidance and implementation mapping informs the policy dialogue and is critical to reducing the time lag between scientific discovery and the provision of life-saving HIV services.

METHODS After disseminating the recommendations, the WHO and UNAIDS have developed and updated databases of national HIV/AIDS and TB guidelines19,20 using a internet-based search for guidelines and by contacting officials in Ministries of Health, UNAIDS and WHO regional offices, and the United States Centers for Disease Control and Prevention. From these databases, which are available online, we reviewed the latest ART, TB and HIV-TB guidelines for the top 24 high HIV-TB countries accounting for an estimated 89% of all HIV-positive incident TB cases in 20124 (last accessed on 30 January 2014). As guidelines for the Russian Federation were not available, that country was excluded from further analysis; our study was thus limited to the remaining 23 countries (Table 1). Using a standard data collection form, we reviewed recommendations on 1) ART eligibility criteria for asymptomatic PLHIV, 2) ART eligibility criteria for HIV-infected TB patients, 3) recommendations on ICF, 4) TB exclusion criteria for IPT initiation, 5) duration of IPT, 6) exceptions to IPT, 7) measures for TB infection control, and 8) HIV counselling and testing for TB patients. To evaluate the status of programme implementation, we reviewed the 2012 data on the following key indicators from the WHO global tuberculosis control report 20134 and the UNAIDS Report on the Global AIDS Epidemic 20135: 1) estimated HIV-positive incident TB cases, 2) estimated deaths among HIVpositive incident TB cases, 3) ART coverage (according to WHO 2013 guidelines), 4) ART coverage (according to WHO 2010 guidelines), 5) TB patients with known HIV status, 6) HIV-positive TB patients on ART, 7) number of HIV-positive people screened for TB, and 8) number of HIV-positive people provided with IPT. As the study design was a review of existing national policies and did not involve the collection of information from individuals, ethical approval was not required for the study.

RESULTS We reviewed 62 guidelines from the 23 countries representing 76% of the global HIV burden and 89% of HIV-associated TB (Table 1). Of the 23 countries, 16 countries were from Africa, six from Asia and one (Brazil) from South America. The earliest published guidelines were from 2006 and the most recent from 2013. Recommendations on HIV testing and counselling for TB patients Of the 23 countries, 15 (65%) countries, representing 79% of the global HIV-TB burden, have recommendations on HIV testing and counselling for patients

HIV-TB policy review for 23 countries

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Table 1 Country-level data on 1) estimated HIV-positive incident TB cases, 2012 and 2) year of publication of national ART and HIVTB guidelines*

Country Brazil Cameroon China Cote d’Ivoire Democratic Republic of Congo Ethiopia India Indonesia Kenya Lesotho Malawi Mozambique Myanmar Namibia Nigeria South Africa Swaziland Tanzania Thailand Uganda Viet Nam Zambia Zimbabwe Total Global

Estimated Year of publication of guidelines Number of Estimated HIV-positive Estimated deaths people living AIDS-related incident among HIV-positive ART HIV-TB TB infection TB with HIV deaths TB cases incident TB cases guidelines guidelines control guidelines guidelines

31 000

16 000 19 000 7 300 8 800

2 500 7 700 1 200 2 500

2013 2012 2010 2005

480 000 760 000 2 100 000 610 000 1 600 000 360 000 1 100 000 1 600 000 200 000 220 000 3 400 000 6 100 000 210 000 1 500 000 440 000 1 500 000 260 000 1 100 000 1 400 000

32 000 47 000 140 000 27 000 57 000 15 000 46 000 77 000 12 000 5 000 240 000 240 000 5 500 80 000 21 000 63 000 12 000 30 000 39 000

16 000 23 000 130 000 7 500 45 000 9 900 16 000 83 000 19 000 7 300 46 000 330 000 13 000 32 000 12 000 35 000 9 300 35 000 55 000

6 300 5 600 42 000 2 100 7 700 1 500 3 500 45 000 4 600 1 600 19 000 88 000 4 300 7 000 2 200 9 200 2 100 7 600 18 000

2010 2013 2011† 2011 2011 2010 2011 2012 2011 2010† 2010 2013 2010 2012 2010 2013 2011 2013 2013

26 770 000 35 300 000

1 254 500 1 600 000

975 100 1 100 000

291 200 320 000

600 000 780 000 450 000

35 000

2010

2007 2009 2007 2006

2009 2010

2008 2010

2009

2012

2008 2010

2009 2008 2007 2008

2008 2010 2007, 2011‡ 2008 2008 2006 2010 2010

2010 2008 2007 2011 2008

2011 2010 2009

2011

2010

2006

2008 2010

*Source: WHO Global TB Report 2013;4 UNAIDS Report on the Global AIDS Epidemic 2013.5 † India and Namibia issued new ART guidelines in 2013 (these were unavailable at time of review). Note: Guidelines were last accessed on 30 January 2014. ‡ Swaziland ICF/IPT guidelines, 2011. HIV ¼ human immunodeficiency virus; TB ¼ tuberculosis; ART ¼ antiretroviral therapy; AIDS ¼ acquired immune-deficiency syndrome; WHO ¼ World Health Organization; UNAIDS ¼ Joint United Nations Programme on HIV/AIDS; ICF ¼ intensified case finding; IPT ¼ isoniazid preventive therapy.

with presumptive and diagnosed TB. While 11 (48%) countries (Ethiopia, Kenya, Malawi, Namibia, Nigeria, South Africa, Swaziland, Tanzania, Uganda, Zambia and Zimbabwe) recommend provider-initiated counselling and testing (PITC), India, Indonesia and Mozambique recommend voluntary HIV counselling and testing (VCT). Indonesia and India also recommend HIV risk assessment for TB patients before offering VCT in concentrated epidemic areas and routine HIV testing for all TB patients in generalised epidemic areas. Lesotho does not specify its model for providing HIV testing and counselling in TB patients. The number of notified TB patients with a documented HIV test result reached 2.2 million (79% of notified cases) in the 23 countries in 2012.4 HIV testing rates for TB patients were particularly high in the African countries, with more than 80% of notified TB patients tested for HIV in 14 countries in 2012. However, performance was lower in Myanmar and Indonesia, where respectively 13% and 61% of TB patients had a documented HIV result (Appendix Table).* Although 34% of TB * The Appendix is available in the online version of this article, at http://www.ingentaconnect.com/content/iuatld/ijtld/2014/ 00000018/00000010/art00005.

patients in China were tested for HIV in 2012, HIV testing coverage among TB patients was 88% in the 294 Chinese counties with the highest HIV-TB burden.4 ART eligibility criteria for asymptomatic people In July 2013, the WHO recommended ART at CD4 count 6500 cells/mm3. Brazil revised its guidelines in November 2013 to recommend ART for all PLHIV, irrespective of CD4 count. In the same year, Ethiopia, Uganda, Zambia and Zimbabwe (with 13% of the global HIV-TB burden) updated their guidelines to recommend ART at CD4 count 6500 cells/mm3. Guidelines in 16 (70%) of the 23 countries are consistent with the previous (2010) WHO ART guidelines, and recommend initiation of ART at CD4 count 6350 cells/mm3 for asymptomatic people. The remaining two countries (Cameroon and Cote d’Ivoire) recommend starting ART at CD4 count 6200 cells/mm3. In addition, Cameroon ‘considers’ ART for people with CD4 counts of 200–350 cells/mm3. In 2012, Kenya, Namibia, South Africa, Swaziland, Zambia and Zimbabwe had 780% ART coverage using the WHO 2010 eligibility criteria of CD4 count 6350 cells/mm3.21 However, in six (26%) countries,

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less than half of those eligible for ART were receiving it in 2012. Using 2013 WHO guidelines, the coverage of ART ranged from 6% in Indonesia to 61% in Thailand (Appendix Table). ART eligibility criteria for people with HIV and TB Of the 23 countries, guidelines from 20 (87%) countries with 84% of the global HIV-TB burden are consistent with WHO guidelines and recommend ART irrespective of CD4 count for persons with HIV-associated TB. Myanmar recommended ART at a CD4 count of 6500 cells/mm3 for persons with HIV-associated TB, and irrespective of CD4 count for those with drug-resistant TB. Guidelines from Thailand, released after the WHO 2010 guidelines and before those published in 2013, recommend ART at CD4 count 6350 cells/mm3 for TB patients. Guidelines from Cote d’Ivoire did not mention ART eligibility criteria for people with HIV and TB. The 2012 ART coverage rates among PLHIV newly diagnosed with TB remained significantly below overall ART coverage rates (using WHO 2010 eligibility) in all countries (Figure 1). In Namibia, South Africa, Swaziland, Thailand and Zambia, where WHO 2010 ART coverage rates among PLHIV were 775% (WHO 2013 coverage 38–46%), coverage rates for HIV-positive TB patients were ,50%. Only three countries (Brazil, Kenya and Malawi) were delivering ART in 2012 to .55% of HIV-positive TB patients.

Interventions to reduce the burden of tuberculosis in people living with HIV While 22 (96%) countries recommend ICF for TB for all PLHIV, IPT is recommended in 16 (70%) countries. Only 14 (61%) countries have recommendations on TB infection control interventions in their guidelines.

Intensified tuberculosis case finding All countries except Cote d’Ivoire have recommendations on TB screening for PLHIV. A total of 18 (78%) countries recommend using clinical screening for TB symptoms and further diagnosis for patients where TB is suspected. Kenya also recommends community-based TB screening for PLHIV and their family members. China recommends clinical screening using annual chest X-ray (CXR), while Brazil recommends screening with annual TST in those without a previous history of TST positivity. Although Cameroon and the Democratic Republic of Congo (DRC) recommend regular TB screening, they do not mention a specific screening/diagnostic algorithm. Of the 35.3 million PLHIV globally, nearly 4.1 million were reported as being screened for TB in 2012. In the 12 of the 23 countries reporting data, nearly 3.9 million were screened for TB.4,5 As a result of recent efforts in integrated counselling and testing centres and ART centres, 1.3 of the 2.1 million (63%) PLHIV in India were screened for TB in 2012.4,22

Figure 1 ART coverage per WHO 2010 guidelines (%) in 2012 among people living with HIV and HIV-positive TB patients in 23 countries. Note: ART coverage is according to WHO 2010 guidelines (CD4 count 6350 cells/mm3 for asymptomatic people living with HIV and irrespective of CD4 count for all HIV-positive TB patients). HIV ¼ human immunodeficiency virus; ART ¼antiretroviral therapy; WHO ¼ World Health Organization; DRC ¼ Democratic Republic of Congo.


Isoniazid preventive therapy Published guidelines from 16 (70%) countries, accounting for 67% of the global HIV-TB burden, recommend using IPT for TB prevention among PLHIV. The seven (30%) countries that do not explicitly recommend IPT are China, Cote d’Ivoire, DRC, India, Indonesia, Myanmar and Zimbabwe. The criteria for ruling out active TB disease before starting IPT differ across the 16 countries. The most recent guidelines for 12 countries recommend symptom-based screening to determine eligibility for IPT (Figure 2). Ethiopia, Kenya, Malawi, Uganda and Zambia recommend the four-symptom screening algorithm, consistent with the 2011 WHO ICF/IPT guidelines. While four-symptom screening was recommended in the 2008 HIV-TB guidelines from Ethiopia, the remaining four countries adopted the recommendation after the release of the 2011 WHO ICF/IPT guidelines. The other seven countries recommend that additional clinical symptoms such as chest pain, loss of appetite, enlarged glands or nodes and shortness of breath should be excluded before starting IPT. Brazil and Cameroon do not mention symptom screening and recommend only TST for IPT initiation for TST-positive persons and TST-negative individuals in close contact with TB patients. In Cameroon, IPT is also recommended for TST-negative individuals with CD4 count 6200 cells/mm3. South Africa recommends symptom screening combined with TST, while Nigeria recommends symptom screening and chest radiography. Guidelines in 15 countries are consistent with WHO guidelines, and recommend IPT for at least 6

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months. In Malawi, IPT is recommended for as long as a person is in ‘pre-ART’ follow-up. IPT for 6 months is recommended in 10 countries. The duration of IPT is 6–9 months in Lesotho and Tanzania, 9 months in Viet Nam and 12 months in Uganda. South Africa recommends IPT for 1) at least 36 months for TST-positive persons, 2) 6 months for those with unknown TST results or persons with negative results and CD4 count .350 cells/mm3, and 3) 12 months for persons with negative results who are receiving ART. Among the nine countries that reported data, approximately 476 000 persons newly registered in HIV care in 2012 initiated IPT. Provision of IPT has increased steadily, particularly in South Africa, Namibia, Malawi and Mozambique.4,23 However, despite this progress and the existence of published guidelines, the level of programme implementation of IPT was limited in at least eight of the 16 countries recommending the use of IPT (Figure 3). In these countries, fewer than 10 000 people were receiving IPT in 2012, or IPT programmes were in pilot or early implementation phase.

Tuberculosis infection control Of the 23 countries, 14 (61%) recommend various interventions for TB infection control in health care facilities. There were 11 TB infection control guidelines, and recommendations on TB infection control were integrated in ART guidelines for five countries and HIV-TB guidelines for six countries. Thirteen countries recommend various administrative, environmental and personal protective measures for TB infection control. Guidelines from

Figure 2 TB screening and diagnosis algorithm for TB exclusion before IPT initiation in 16 countries. Note: Countries recommend that IPT be given if the screening tests allow for IPT and if none of the symptoms tested are present. WHO ¼ World Health Organization; TST ¼ tuberculin skin test; TB ¼ tuberculosis; IPT ¼ isoniazid preventive therapy.

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Figure 3 Map showing the policy on and status of implementation of IPT in the 23 high HIV and TB burden countries. Note: Implementation or availability of IPT is considered limited in countries where ,10 000 people are receiving IPT or the programme is in the pilot or early implementation phase. Source: WHO Global TB Report 2013;4 UNAIDS Report on the Global AIDS Epidemic 2013.5 IPT ¼ isoniazid preventive treatment; TST ¼ tuburculin skin test; HIV ¼ human immunodeficiency virus; TB ¼ tuberculosis.

Indonesia recommend isolation and TB screening of PLHIV. No country systematically collects data on the implementation of TB infection control interventions. Assessment of TB transmission risk is conducted at facility level in five countries; India, Thailand and Indonesia report demonstrable infection control practices in the majority of their ART centres.22,24,25

DISCUSSION HIV has fuelled the resurgence of the TB epidemic and is a major obstacle to achieving the global HIV and TB targets set out in the 2011 UN Political Declaration on HIV/AIDS6 and the Millennium Development Goals. Specifically, reaching the 2011 UN High-Level Meeting target of reducing HIVassociated TB mortality by 50% will require efforts to prevent and treat both HIV and TB. Launched in 2005, the WHO’s Stop TB Strategy goes beyond DOTS expansion and recognises the increasing need to scale up HIV testing, earlier administration of ART and the Three I’s for HIV/TB.26 Our review found that, at the end of 2013, guidelines in 16 of the 23 countries are consistent with the 2010 WHO ART recommendations for asymptomatic persons and HIV-positive TB patients. Furthermore, seven countries have changed recommendations or are planning to adapt their guidelines to the WHO 2013 ART guidelines, which establish a new global standard (Table 2). The new 2013 WHO

recommendations further enhance TB prevention by recommending earlier ART at CD4 count 6500 cells/ mm3, combined with other new ‘test and treat’ indications (e.g., ART, irrespective of CD4 count for the HIV-positive partner in a serodiscordant couple, TB patients, hepatitis B patients and children aged ,5 years). However, despite the significant potential prevention benefits, implementation of the WHO 2010 and 2013 guidelines continues to pose significant challenges. Using the older, more conservative WHO 2010 eligibility criteria, ART coverage in 2012 was ,60% in many high HIV-TB burden countries.5 Using the WHO 2013 guidelines translates to an even lower ART coverage figure, of ,40%, in at least 15 countries. This lower access to ART includes a significant number of PLHIV who are still at high risk of TB-related morbidity and mortality. Similarly, ART coverage among HIV-positive TB patients was ,40% in at least 14 countries.23 Based on an analysis from the Stop TB Partnership, major challenges to ART scale-up among HIV-positive TB patients include non-availability of ART at TB facilities, poor linkages between TB and ART sites, and the relative centralisation of ART services compared to TB services.27 Although IPT has been recommended for PLHIV by the WHO since 1999, seven of the high-burden countries in our review have yet to adopt IPT as a national policy. Others are still developing strategies for the implementation of IPT,28 and at least four countries have pilot programmes to determine the


Table 2

Review of national guidelines on ART, HIV testing for TB patients and TB prevention in people living with HIV

Country Brazil Cameroon China Cote d’Ivoire Democratic Republic of Congo Ethiopia India Indonesia Kenya Lesotho Malawi Mozambique Myanmar Namibia Nigeria South Africa Swaziland Tanzania Thailand Uganda Viet Nam Zambia Zimbabwe

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ART at CD4 count 6500 cells/mm3 Yes (irrespective of CD4 count) No No No No

ART coverage (2013 WHO guidelines) %

ART for all people with HIV-associated TB

Recommendation on HIV testing for TB patients

Yes

*

Yes* Yes*

*

30 12

Yes*

Yes No† No No No No No No No† No No No No No

35 30 6 42 31 39 39 29 53 15 38 42 31 61

Yes No Yes Yes

29 28 46 47

23

IPT is national policy

TST (or chest X-ray) is required before IPT

Yes

Yes Yes

*

Yes* No No No

Yes* Yes* Yes* Yes Yes* Yes Yes* No* Yes* Yes* Yes* Yes* Yes* No*

PITC* VCT* VCT* PITC Recommended PITC VCT * PITC PITC PITC PITC PITC *

Yes No No Yes* Yes Yes Yes No Yes Yes* Yes Yes* Yes* Yes*

No

Yes* Yes* Yes* Yes*

PITC * PITC PITC

Yes* Yes* Yes* No

No No No No No Yes Yes No No No (but provided to TST-positive) No No No

*Represents limited availability or implementation (defined as ,50% ART coverage for persons with HIV-associated TB and ,80% HIV testing rate for TB patients). † India and Namibia have reported guidelines revision in 2013 recommending ART at CD4 count 6500 cells/mm3. ART ¼antiretroviral therapy; HIV ¼ human immunodeficiency virus; TB ¼ tuberculosis; WHO ¼ World Health Organization; IPT ¼ isoniazid preventive therapy; TST ¼ tuberculin skin test; PITC ¼ provider-initiated counselling and testing; VCT ¼ voluntary counselling and testing.

operational feasibility and acceptability of IPT.22,29,30 Furthermore, recording and reporting data on ICF and IPT is a challenge in many countries. The data show that although availability of TB screening for PLHIV and IPT has increased significantly, coverage of these interventions is still limited in many countries.23 Further progress is needed to screen everyone enrolled in HIV care for symptoms of TB and to provide IPT to all those eligible by 2015. While the TB prevention focus is on improving early access for asymptomatic PLHIV to ART and IPT, improved TB screening could facilitate increased TB case finding among PLHIV and appropriate initiation of ART among PLHIV who would otherwise not be eligible for ART based on CD4 count. National policies that are consistent with WHO guidelines and promote access to early ART and the Three I’s for HIV/TB are likely to improve health outcomes for PLHIV. Using the guideline review process,31 WHO guidelines take into consideration available scientific evidence, cost, feasibility and the values and preferences of the community and health care workers. Country programmes are often guided by the WHO and other international guidelines, latest scientific evidence and programmatic and operational research when formulating their national guidelines. However, national guidelines take considerable time to translate new evidence into policy, and the

eligibility criteria for ART and IPT vary significantly among countries. Policy adaptation can be a complex and lengthy process, and it is clear from our review that additional efforts will be needed to reduce the delay between scientific discovery and service delivery. There is also a need for innovation in service delivery models to ensure that people have access to life-saving HIV and TB services, as emphasised by Treatment 2015.32 Linking and integrating HIV and TB services could lower access barriers and ensure that many more PLHIV are screened for TB, offered IPT or diagnostic tests for TB, and ART (if eligible), that persons in TB care are tested for HIV and that those testing positive are offered ART as early as possible under national guidelines. There has been considerable progress in this area, and all ART facilities in Kenya, Mozambique, South Africa and Zimbabwe provide TB-related services for PLHIV. The majority of the ART centres in Nigeria and Swaziland and HIV testing and counselling facilities in South Africa have also integrated TB services in their care packages.27 Brazil and Myanmar have developed plans to scale up the availability of TB services at all facilities providing HIV care.33,34 TB services and maternal and child health care services are often decentralised, and in many settings could facilitate access to HIV care and treatment at

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peripheral-level health care facilities. For example, HIV-TB services in Namibia can be accessed in maternal and child health care settings.35 The call by the Global Fund for a single concept note proposal for HIV and TB for high-burden countries should further facilitate integration and collaboration between these critical programmes.36 While effective linkages between existing HIV and TB services are being established, some countries are also innovating service delivery by expanding HIV and TB testing to communities through home-based testing and multidisease prevention campaigns. For example, in 2010–2011, South Africa conducted a massive HIV testing and counselling campaign where more than 13 million and 8 million people, respectively, were screened for HIV and TB.21 South Africa also implemented an active case-finding programme in 2011 to trace all persons diagnosed with TB, screen their family members for TB and counsel them for HIV testing at home. The programme had reached 180 000 households by 2012.37 Similarly, Kakyerere community health campaigns in southwestern Uganda are rolling out HIV VCT along with multi-disease care for thousands of people over a few days.38,39 These innovative approaches, which rely on strengthening facility-based systems to meet increased demand, have been highly successful in reaching large populations and are recommended in the 2013 WHO ART guidelines.15 Treatment 201532 also emphasises the concept of speed, and it is clear from our policy review that the current rate of expansion needs to accelerate to avoid leaving millions of people without the significant benefits of HIV and TB prevention interventions. TB is an airborne disease, and each person with smearpositive pulmonary TB infects around 10–15 other persons each year.40 Delays in preventing HIVassociated TB result in additional cases of TB, both drug-susceptible and multidrug-resistant, which further complicate efforts to save lives and control TB. Specifically, countries will need to adapt their guidelines more rapidly to maximise preventive and clinical impact and to map services to ensure that they reach all PLHIV. Our policy review has some limitations. Although we conducted a thorough search for the latest published national guidelines, some might have been out of date or in the process of being updated since the recent release of the 2013 WHO ART guidelines. Furthermore, other guidelines with recommendations for HIV testing and the Three I’s for HIV-TB may not have been identified by our search strategy. In addition, we only looked at recommendations on ART, HIV testing for TB patients and the Three I’s for HIV-TB. Policy recommendations on other HIV-TB collaborative activities to reduce the burden of HIV in patients with TB and activities to establish and strengthen mechanisms for delivering integrated TB-

HIV services were not analysed. We used published guidelines for our analysis, and in some cases programme and clinical practice may differ. We relied on routine reporting on country-level programme implementation to assess the implementation of national guidelines. Further efforts are needed to monitor the extent of implementation of the current guidelines and evaluate country experiences in scaling up ART, HIV and TB screening and IPT.

CONCLUSION The WHO 2013 ART guidelines reflect evolving evidence showing that early initiation of ART is costeffective, improves health outcomes, prevents HIVassociated TB and reduces HIV transmission. Along with earlier initiation of ART, the Three I’s for HIV/ TB have been recognised as key interventions for reducing the TB burden in PLHIV. Policy development and adaptation is a dynamic process, and some countries have already integrated or are in the process of integrating the WHO 2013 recommendations into their national HIV and TB policies. Others, such as Uganda, have used the new science around treatment as prevention to provide earlier treatment by adding additional ART eligibility criteria for commercial sex workers, truck drivers or fishermen.41 However, for many settings the slow implementation of existing guidance and adoption of new scientific evidence is a missed opportunity for the prevention of illness, death and transmission among PLHIV and their communities. Increased efforts are needed to accelerate policy adaptation and implementation to effectively link and integrate the delivery of HIV and TB services so that people in need have timely access to these life-saving HIV-TB interventions. As part of the Treatment 2015 initiative, UNAIDS, in collaboration with stakeholders, will continue to play a pro-active role in addressing the closely linked HIV and TB coepidemics by supporting the scale-up of comprehensive integrated HIV-TB prevention strategies.42 Acknowledgements The authors appreciate the contribution of experts from UNAIDS and World Health Organization (Geneva, Switzerland) regional offices, the US Centers for Disease Control and Prevention (CDC, Atlanta, GA, USA), and the Ministries of Health in providing us with the latest guidelines and their valuable inputs on policy recommendations. The opinions and statements in this article are those of the authors and do not represent the official policy, endorsement or views of UNAIDS or CDC. Conflicts of interest: none declared.

References 1 Harries A D, Zachariah R, Corbett E L, et al. The HIVassociated tuberculosis epidemic—when will we act? Lancet 2010; 375: 1906–1919. 2 Dye C, Scheele S, Dolin P, Pathania V, Raviglione M C.


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17

18

Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 1999; 282: 677– 686. Getahun H, Gunneberg C, Granich R, Nunn P. HIV infectionassociated tuberculosis: the epidemiology and the response. Clin Infect Dis 2010; 50 (Suppl 3): S201–S207.4 World Health Organization. Global tuberculosis report, 2013. WHO/HTM/TB/2013.11. Geneva, Switzerland: WHO, 2013. http://apps.who.int/iris/bitstream/10665/91355/1/ 9789241564656_eng.pdf. Accessed May 2014. Joint United Nations Programme on HIV/AIDS. UNAIDS report on the global AIDS epidemic 2013. UNAIDS/JC2502/ 1/E. Geneva, Switzerland: UNAIDS, 2013. http://www.unaids. org/en/media/unaids/contentassets/documents/epidemiology/ 2013/gr2013/UNAIDS_Global_Report_2013_en.pdf. Accessed May 2014. United Nations General Assembly. Political declaration on HIV and AIDS 2011. A/RES/65/277. New York, NY, USA: UN, 2011. http://www.unaids.org/en/media/unaids/contentassets/ documents/document/2011/06/20110610_UN_A-RES-65277_en.pdf. Accessed May 2014. World Health Organization. Policy on collaborative TB/HIV activities: guidelines for natinal programmes and other stakeholders. WHO/HTM/TB/2012.1. WHO/HIV/2012.1. Geneva, Switzerland: WHO, 2012. http://whqlibdoc.who.int/publications/2012/9789241503006_eng.pdf. Accessed May 2014. Miranda A, Morgan M, Jamal L, et al. Impact of antiretroviral therapy on the incidence of tuberculosis: the Brazilian experience, 1995–2001. PLOS ONE 2007; 2: e826. Middelkoop K, Bekker L G, Myer L, et al. Antiretroviral therapy and TB notification rates in a high HIV prevalence South African community. J Acquir Immune Defic Syndr 2011; 56: 263–269. Girardi E, Antonucci G, Vanacore P, et al. Impact of combination antiretroviral therapy on the risk of tuberculosis among persons with HIV infection. AIDS 2000; 14: 1985– 1991. Lawn S D, Harries A D, Williams B G, et al. Antiretroviral therapy and the control of HIV-associated tuberculosis. Will ART do it? Int J Tuberc Lung Dis 2011; 15: 571–581. Suthar A B, Lawn S D, Del Amo J, et al. Antiretroviral therapy for prevention of tuberculosis in adults with HIV: a systematic review and meta-analysis. PLOS Med 2012; 9: e1001270. World Health Organization. Antiretroviral treatment as prevention (TASP) of HIV and TB. WHO/HIV/2012.12. Geneva, Switzerland: WHO, 2012. http://whqlibdoc.who.int/hq/2012/ WHO_HIV_2012.12_eng.pdf. Accessed May 2014. World Health Organization. Antiretroviral therapy for HIV infection in adults and adolescents. Geneva, Switzerland: WHO, 2010. http://whqlibdoc.who.int/publications/2010/ 9789241599764_eng.pdf. Accessed May 2014. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Geneva, Switzerland: WHO, 2013. http://apps.who. int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf. Accessed May 2014. Grinsztejn B, Hosseinipour M C, Ribaudo H J, et al. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial. Lancet Infect Dis 2014; 14: 281–290. World Health Organization. Guidelines on intensified tuberculosis case finding and isoniazid preventive therapy for people living with HIV in resource constrained setting. Geneva, Switzerland: WHO, 2011. http://whqlibdoc.who.int/publications/2011/9789241500708_eng.pdf. Accessed May 2014. World Health Organization. WHO policy on TB infection control in health-care facilities, congregate settings and

19

20

21

22

23

24

25

26 27

28

29

30

31

32

1157

households. WHO/HTM/TB/2009.419. Geneva, Switzerland: WHO, 2009. http://whqlibdoc.who.int/publications/2009/ 9789241598323_eng.pdf. Accessed May 2014. Joint United Nations Programme on HIV/AIDS. The Global Database of National HIV/AIDS guidelines. Geneva, Switzerland: UNAIDS, 2014. World Health Organization. Online database of national HIV and TB guidelines. Geneva, Switzerland: WHO, 2011. http:// www.who.int/hiv/pub/national_guidelines/en/index.html. Accessed May 2014. World Health Organization, United Nations International Childrens’ Emergency Fund and Joint United Nations Programme on HIV/AIDS. Global update on HIV treatment 2013: results, impact and opportunities. Geneva, Switzerland: UNAIDS, 2013. http://www.unaids.org/en/media/unaids/ contentassets/documents/unaidspublication/2013/20130630_ treatment_report_en.pdf. Accessed May 2014. National AIDS Control Organization, Department of AIDS Control India. Annual report 2012-13. New Delhi, India: NACO, 2013. http://www.naco.gov.in/upload/Publication/ Annual%20Report/Annual%20report%202012-13_English. pdf Accessed July 2014 World Health Organization. Global tuberculosis report, 2012. WHO/HTM/TB/2012.6. Geneva, Switzerland: WHO, 2012. http://apps.who.int/iris/bitstream/10665/75938/1/ 9789241564502_eng.pdf. Accessed May 2014. Joint United Nations Programme on HIV/AIDS. Thailand AIDS response progress report 2012. Geneva, Switzerland: UNAIDS, 2 0 1 2 . h t t p : / / w w w. u n a i d s . o r g / e n / d a t a a n a l y s i s / knowyourresponse/countryprogressreports/2012countries/ce_ TH_Narrative_Report%5B1%5D.pdf. Accessed May 2014. Republic of Indonesia. Country report on the follow up to the Declaration of Commitment on HIV/AIDS (UNGASS). reporting period 2010–2011. Jakarta, Indonesia: Indonesian National AIDS Commission, 2012. http://www.unaids.org/en/ dataanalysis/knowyourresponse/countryprogressreports/ 2012countries/ce_ID_Narrative_Report.pdf. Accessed May 2014. Raviglione M C, Uplekar M W. WHO’s new Stop TB Strategy. Lancet 2006; 367: 952–955. World Health Organization, Stop TB Department. Summary of key TB/HIV indicators, progress so far, challenges and gaps, opportunities and actions in 10 countries. Geneva, Switzerland: WHO, 2012. Joint United Nations Programme on HIV/AIDS. Global AIDS response progress report 2012. Zimbabwe country report. Geneva, Switzerland: UNAIDS, 2012. http://www.unaids.org/ en/dataanalysis/knowyourresponse/countryprogressreports/ 2012countries/ce_ZW_Narrative_Report.pdf. Accessed May 2014. Ministry of Health of the People’s Republic of China. AIDS response progress report 2012. Beijing, China: Moh, 2012. http://www.unaids.org/en/dataanalysis/knowyourresponse/ countryprogressreports/2012countries/ce_CN_Narrative_ Report%5B1%5D.pdf. Accessed May 2014. World Health Organization Regional Office for South-East Asia. Report of the workshop to accelerate the implementation of TB-HIV collaborative activities in SEAR. SEA-TB-342. New Delhi, India: WHO, 2012. http://apps.searo.who.int/pds_docs/ B4910.pdf. Accessed May 2014. World Health Organization Guidelines Review Committee (GRC). Geneva, Switzerland: WHO, 2014. http://www.who. int/kms/guidelines_review_committee/en/index.html. Accessed May 2014. Joint United Nations Programme on HIV/AIDS. Treatment 2015. Geneva, Switzerland 2013. Geneva, Switzerland: UNAIDS, 2013. http://www.unaids.org/en/media/unaids/ contentassets/documents/unaidspublication/2013/JC2484_ treatment-2015_en.pdf. Accessed May 2014.

1158


33 Brazilian Ministry of Health, Health Surveillance Secretariat, Department of STD, AIDS and Viral Hepatitis. Progress Report on the Brazilian Response to HIV/AIDS (2010–2011). Brasilia, Brazil: MoH, 2012. http://www.unaids.org/en/dataanalysis/ knowyourresponse/countryprogressreports/2012countries/ UNGASS_2012_ingles_rev_08jun.pdf. Accessed May 2014. 34 Joint United Nations Programme on HIV/AIDS. Global AIDS response progress report 2012: Myanmar. Geneva, Switzerland: UNAIDS, 2012. http://www.unaids.org/en/dataanalysis/ knowyourresponse/countryprogressreports/2012countries/ce_ MM_Narrative_Report.pdf. Accessed May 2014. 35 World Health Organization. Workshop to scale up the implementation of Collaborative TB/HIV activities in Africa. Maputo, Mozambique 2013. Geneva, Switzerland: WHO, 2013. http://www.who.int/tb/challenges/hiv/implementation_ workshop_report.pdf. Accessed May 2014. 36 The Global Fund To Fight AIDS, Tuberculosis and Malaria. The Global Fund new funding model. Geneva, Switzerland: The Global Fund, 2014. http://www.theglobalfund.org/en/ fundingmodel/. Accessed May 2014. 37 Republic of South Africa. Global AIDS response progress report 2012. Pretoria, South Africa: MoH South Africa, 2012. http://www.unaids.org/en/dataanalysis/knowyourresponse/

38

39

40 41

42

countryprogressreports/2012countries/ce_ZA_Narrative_ Report.pdf. Accessed May 2014. Chamie G, Kwarisiima D, Clark T D, et al. Uptake of community-based HIV testing during a multi-disease health campaign in rural Uganda. PLOS ONE 2014; 9: e84317. Chamie G, Kwarisiima D, Clark T D, et al. Leveraging rapid community-based HIV testing campaigns for non-communicable diseases in rural Uganda. PLOS ONE 2012; 7: e43400. Musher D M. How contagious are common respiratory tract infections? N Engl J Med 2003; 348: 1256–1266. Ministry of Health, The Republic of Uganda. Addendum to the national antiretroviral treatment guidelines for Uganda. Kampala, Uganda: MoH, 2013. http://www.kisiizihospital.org.ug/ wp-content/uploadedfiles/2013/10/Addednum-National-ARTRx-Guidelines-Dec-2013.pdf. Accessed May 2014. UNAIDS and Stop TB Partnership. Memorandum of Understanding between the Secretariat of the Joint United Nations Programme on HIV/AIDS and the Stop TB Partnership to achieve zero deaths from TB among people living with HIV. Geneva, Switzerland: WHO, 2012. http://www.stoptb.org/ assets/documents/about/cb/meetings/22/2.12-02 Report of the Executive Secretary/2.12-2.3 Stop TB & UNAIDS MoU.pdf. Accessed May 2014.

— 49 — 55

38 68 51 18 81 59 76 48 46 91 36 81 87 68 76 70 58 86 85

307 025 117 791 151 519 104 750

59 468 270 460 570 620 29 960 548 588 87 352 368 690 282 687 49 676 105 347 459 465 2 010 340 80 103 399 886 232 816 403 089 68 883 446 841 518 801

ART coverage (WHO 2010 guidelines) %

12 35 30 6 42 31 39 39 29 53 15 38 42 31 61 29 28 46 47

— 23 — 30

ART coverage (WHO 2013 guidelines) %

35 000 96 000 822 000 2 700 93 000 10 000 19 000 48 000 19 000 9 900 83 000 294 000 7 400 52 000 44 000 41 000 68 000 45 000 34 000

46 000 21 000 309 000 21 000 (31) (65) (56) (0.8) (94) (88) (93) (94) (13) (89) (84) (84) (95) (82) (72) (86) (66) (100) (88)

(55) (82) (34) (85)

TB patients with known HIV status (% of TB patients with known HIV status) n (%) (57) (22) (47) (30)

2 296 (14) 8 022 (35) 25 790 (20) 4 209 (—) 26 487 (59) 4 171 (42) 9 144 (57) 15 391 (19) 4 270 (22) 3 362 (46) 10 866 (24) 101 937 (31) 3 762 (29) 10 993 (34) 3 591 (30) 9 962 (28) 2 232 (24) 14 471 (41) —

9 049 4 261 3 454 2 396

HIV-positive TB patients on ART (% of the estimated HIV-positive incident TB cases) n (%)

— 272 000 1 324 000 23 000 — 21 000 393 000 — — 12 000 140 000 950 000 69 000 357 000 — — — — —

— 12 000 295 000 —

Number of HIV-positive persons screened for TB

— 30 000 — — — 16 000 21 000 17 000 — 12 000 2 300 370 000 1 900 — — — 5 700 — —

— — — —

Number of HIV-positive persons provided IPT

* Source: WHO Global TB Report 2013;4 UNAIDS Report on the Global AIDS Epidemic 2013.5 HIV ¼ human immunodeficiency virus; TB ¼ tuberculosis; ART ¼antiretroviral therapy; WHO ¼ World Health Organization; IPT ¼ isoniazid preventive therapy; UNAIDS ¼ Joint United Nations Programme on HIV/AIDS.

Brazil Cameroon China Cote d’Ivoire Democratic Republic of Congo Ethiopia India Indonesia Kenya Lesotho Malawi Mozambique Myanmar Namibia Nigeria South Africa Swaziland Tanzania Thailand Uganda Viet Nam Zambia Zimbabwe

Country

Reported number of persons on ART

Table Country-level programme data on HIV testing for TB patients, ART coverage for people living with HIV, ART coverage for TB patients and provision of the Three I’s for HIV-TB (for the year 2012)*

APPENDIX


i

ii


RESUME

La publication d’un guide de politique nationale est une e´ tape critique pour assurer une bonne coordination VIH-TB (virus de l’immunode´ ficience humainetuberculose) et une bonne mise en œuvre du programme. Grace ˆ a` la base de données du programme commun des Nations Unies sur le VIH/SIDA (ONUSIDA) (accès en janvier 2014), nous avons revu 62 directives nationales sur le VIH et la TB dans 23 pays lourdement touchés pour y trouver les recommandations relatives au test VIH des patients tuberculeux, aux critères de mise en œuvre du traitement antirétroviral (ART) et aux Trois I du VIH/TB (traitement préventif par isoniazide [IPT], intensification de la recherche de cas de TB et la lutte contre l’infection tuberculeuse). Nous avons utilisé les données par pays de l’ONUSIDA afin de déterminer l’état de la mise en œuvre des directives existantes. Sur les 23 pays représentant 89% du fardeau mondial du VIH-TB, le Brésil recommande l’ART sans tenir compte de la numération des CD4 pour toutes les personnes vivant avec le VIH, et 4 pays (17%) recommandent l’ART selon les directives 2013 de l’Organisation Mondiale de la Sant e´ (OMS) en 6500 fonction du niveau des CD4, c’est-a-dire `

cellules/mm3

pour les patients asymptomatiques. Dixneuf pays (83%) sont en accord avec les directives OMS 2013 et recommendent l’ART pour les patients TB-VIH positifs sans tenir compte du nombre de CD4. L’IPT est recommandé par 16 pays (70%) représentant 67% du fardeau du VIH-TB ; 12 pays recommandent un dépistage basé seulement sur les symptomes ˆ pour la mise en route de l’IPT. Les directives de 15 pays (65%) supportant 79% du fardeau du VIH-TB incluent des recommandations sur le test et le conseil en matière de VIH pour les patients tuberculeux. Bien que la couverture de l’ART, du test VIH pour les patients tuberculeux, du dépistage de la TB chez les personnes vivant avec le VIH et de l’IPT aient significativement augmenté, le progrès reste limité dans de nombreux pays. Il existe une variation considérable dans le délai de mise en œuvre et le contenu des politiques nationales quand on les compare aux directives de l’OMS. Les occasions manquées de mettre en œuvre de nouvelles stratégies scientifiquement prouvées et le retard dans l’adaptation des directives existantes de l’OMS restent un défi majeur pour de nombreux pays.

RESUMEN

La promulgaci on ´ de orientaciones normativas nacionales constituye una etapa primordial en la obtencion ´ de una buena coordinacion ´ de las iniciativas contra la infeccion ´ por el virus de la inmunodeficiencia humana y la tuberculosis (VIH-TB) y en la ejecucion ´ adecuada del programa conjunto. A partir de la base de datos del Programa Conjunto de las Naciones Unidas sobre el VIH/SIDA (ONUSIDA, consultada en enero del 2014), se examinaron 62 orientaciones nacionales sobre el VIH y la TB de 23 pa´ıses con alta carga de morbilidad, con relacion ´ a las recomendaciones sobre la praćtica de la prueba diagnostica ´ del VIH en los pacientes con diagnostico ´ de TB, los criterios de iniciacion ´ del tratamiento antirretrov´ırico (ART) y la iniciativa de las ‘Tres ıés’ (tratamiento preventivo con isoniazida [IPT], busqueda ´ intensiva de casos de TB y control de la infecci on ´ tuberculosa). Los datos nacionales del programa ONUSIDA se usaron con el fin de determinar la situacion ´ de la ejecuci on ´ de las orientaciones existentes. De los 23 pa´ıses que representan el 89% de la carga mundial de morbilidad por VIH-TB, Brasil recomienda el ART independientemente del recuento de células CD4 a todas las personas infectadas por el VIH y cuatro pa´ıses (17%) recomiendan este tratamiento en consonancia con las orientaciones de la Organizacion ´ Mundial de la Salud (OMS) del 2013, a saber, en las personas

asintoma´ticas con un recuento de células CD4 6500 células/mm3. Las recomendaciones de 19 pa´ıses (83%) son acordes con las orientaciones de la OMS del 2013 e indican el ART a los pacientes TB positivos frente al VIH, independientemente del recuento de células CD4. El IPT se recomienda en 16 pa´ıses (70%) que representan el 67% de la carga de morbilidad por VIH-TB; 12 pa´ıses recomiendan la deteccion ´ sistema´tica basada unicamente ´ en los s´ıntomas antes de iniciar el IPT. Las orientaciones de 15 pa´ıses (65%) que representan el 79% de la carga de morbilidad por VIH-TB incluyen recomendaciones en materia de pruebas diagnosticas ´ y orientacion ´ sobre el VIH a los pacientes tuberculosos. Aunque la aceptacion ´ del ART y las pruebas del VIH en pacientes con TB y la deteccion ´ sistema´tica de la TB en los pacientes positivos frente al VIH ha aumentado de manera considerable, los progresos son aun ´ limitados en muchos pa´ıses. Existe una variabilidad notable en materia de coordinacion ´ cronologica ´ y contenido de las pol´ıticas nacionales, cuando se comparan con las orientaciones de la OMS. Las oportunidades desaprovechadas para aplicar los nuevos datos cient´ıficos y el retraso en la adaptacion ´ de las orientaciones vigentes de la OMS constituyen aun un obstaćulo importante en muchos pa´ıses.

HIV policy and implementation: a national policy review and an implementation case study of a rural area of northern Malawi.

Monitoring HIV and AIDS Related Policy Reforms: A Road Map to Strengthen Policy Monitoring and Implementation in PEPFAR Partner Countries.

Global implementation of advanced urological care: Policy implementation research.

Design and Implementation of the Retinoblastoma Collaborative Laboratory.

A mixed-methods study of the implementation of medication adherence policy solutions: how do European countries compare?

Intersectoral policy for severe and persistent mental illness: review of approaches in a sample of high-income countries.

A review of bovine Johne's disease control activities in 6 endemically infected countries.

Effective Implementation of collaborative care for depression: what is needed?

Protocol for regional implementation of collaborative lung function testing.

The development, implementation and evaluation of clinical practice guidelines in Gulf Cooperation Council (GCC) countries: a systematic review of literature.

Design and implementation of a collaborative study of the mutagenicity of complex mixtures in Salmonella typhimurium.

Policy implementation for methicillin-resistant Staphylococcus aureus in seven European countries: a comparative analysis from 1999 to 2015.

The 'problematisation' of palliative care in hospital: an exploratory review of international palliative care policy in five countries.

Status of patient safety culture in Arab countries: a systematic review.

The impact of socioeconomic status on foodborne illness in high-income countries: a systematic review.

Abortion policy and women's health in developing countries.

Providing ethical guidance for collaborative research in developing countries.

Sexual violence in India: addressing gaps between policy and implementation.

The role of partnerships in U.S. Food Policy Council policy activities.

The relationship between iron status and adiposity in women from developing countries: a review.

Socioeconomic position and childhood-adolescent weight status in rich countries: a systematic review, 1990-2013.

Stepped collaborative depression care: primary care results before and after implementation of a stepped collaborative depression programme.

WHO essential medicines policies and use in developing and transitional countries: an analysis of reported policy implementation and medicines use surveys.

HTA Implementation Roadmap in Central and Eastern European Countries.